Loss of mitochondrial Ca2+ uptake protein 3 impairs skeletal muscle calcium handling and exercise capacity.

Mitochondrial calcium concentration ([Ca2+ ]m ) plays an essential role in bioenergetics, and loss of [Ca2+ ]m homeostasis can trigger diseases and cell death in numerous cell types. Ca2+ uptake into mitochondria occurs via the mitochondrial Ca2+ uniporter (MCU), which is regulated by three mitochondrial Ca2+ uptake (MICU) proteins localized in the intermembrane space, MICU1, 2, and 3. We generated a mouse model of systemic MICU3 ablation and examined its physiological role in skeletal muscle. We found that loss of MICU3 led to impaired exercise capacity. When the muscles were directly stimulated there was a decrease in time to fatigue. MICU3 ablation significantly increased the maximal force of the KO muscle and altered fibre type composition with an increase in the ratio of type IIb (low oxidative capacity) to type IIa (high oxidative capacity) fibres. Furthermore, MICU3-KO mitochondria have reduced uptake of Ca2+ and increased phosphorylation of pyruvate dehydrogenase, indicating that KO animals contain less Ca2+ in their mitochondria. Skeletal muscle from MICU3-KO mice exhibited lower net oxidation of NADH during electrically stimulated muscle contraction compared with wild-type. These data demonstrate that MICU3 plays a role in skeletal muscle physiology by setting the proper threshold for mitochondrial Ca2+ uptake, which is important for matching energy demand and supply in muscle. KEY POINTS: Mitochondrial calcium uptake is an important regulator of bioenergetics and cell death and is regulated by the mitochondrial calcium uniporter (MCU) and three calcium sensitive regulatory proteins (MICU1, 2 and 3). Loss of MICU3 leads to impaired exercise capacity and decreased time to skeletal muscle fatigue. Skeletal muscle from MICU3-KO mice exhibits a net oxidation of NADH during electrically stimulated muscle contractions, suggesting that MICU3 plays a role in skeletal muscle physiology by matching energy demand and supply.

Integration of Metabolomics, Lipidomics, and Proteomics Reveals the Metabolic Characterization of Nonalcoholic Steatohepatitis.

Metabolic dysfunction is associated with nonalcoholic steatohepatitis (NASH) development. However, omics studies investigating metabolic changes in NASH patients are limited. In this study, metabolomics and lipidomics in plasma, as well as proteomics in the liver, were performed to characterize the metabolic profiles of NASH patients. Moreover, the accumulation of bile acids (BAs) in NASH patients prompted us to investigate the protective effect of cholestyramine on NASH. The liver expression of essential proteins involved in FA transport and lipid droplets was significantly elevated in patients with NASH. Furthermore, we observed a distinct lipidomic remodeling in patients with NASH. We also report a novel finding suggesting an increase in the expression of critical proteins responsible for glycolysis and the level of glycolytic output (pyruvic acid) in patients with NASH. Furthermore, the accumulation of branched chain amino acids, aromatic amino acids, purines, and BAs was observed in NASH patients. Similarly, a dramatic metabolic disorder was also observed in a NASH mouse model. Cholestyramine not only significantly alleviated liver steatosis and fibrosis but also reversed NASH-induced accumulation of BAs and steroid hormones. In conclusion, NASH patients were characterized by perturbations in FA uptake, lipid droplet formation, glycolysis, and accumulation of BAs and other metabolites.

Antibiofilm Activity and Mechanism of Linalool against Food Spoilage Bacillus amyloliquefaciens.

Pellicle biofilm-forming bacteria Bacillus amyloliquefaciens are the major spoilage microorganisms of soy products. Due to their inherent resistance to antibiotics and disinfectants, pellicle biofilms formed are difficult to eliminate and represent a threat to food safety. Here, we assessed linalool's ability to prevent the pellicle of two spoilage B. amyloliquefaciens strains. The minimum biofilm inhibitory concentration (MBIC) of linalool against B. amyloliquefaciens DY1a and DY1b was 4 µL/mL and 8 µL/mL, respectively. The MBIC of linalool had a considerable eradication rate of 77.15% and 83.21% on the biofilm of the two strains, respectively. Scanning electron microscopy observations revealed that less wrinkly and thinner pellicle biofilms formed on a medium supplemented with 1/2 MBIC and 1/4 MBIC linalool. Also, linalool inhibited cell motility and the production of extracellular polysaccharides and proteins of the biofilm matrix. Furthermore, linalool exposure reduced the cell surface hydrophobicity, zeta potential, and cell auto-aggregation of B. amyloliquefaciens. Molecular docking analysis demonstrated that linalool interacted strongly with quorum-sensing ComP receptor and biofilm matrix assembly TasA through intermolecular hydrogen bonds, hydrophobic contacts, and van der Waals forces interacting with site residues. Overall, our findings suggest that linalool may be employed as a potential antibiofilm agent to control food spoilage B. amyloliquefaciens.

Mutations in non-muscle myosin 2A disrupt the actomyosin cytoskeleton in Sertoli cells and cause male infertility.

Mutations in non-muscle myosin 2A (NM2A) encompass a wide spectrum of anomalies collectively known as MYH9-Related Disease (MYH9-RD) in humans that can include macrothrombocytopenia, glomerulosclerosis, deafness, and cataracts. We previously created mouse models of the three mutations most frequently found in humans: R702C, D1424N, and E1841K. While homozygous R702C and D1424N mutations are embryonic lethal, we found homozygous mutant E1841K mice to be viable. However the homozygous male, but not female, mice were infertile. Here, we report that these mice have reduced testis size and defects in actin-associated junctions in Sertoli cells, resulting in inability to form the blood-testis barrier and premature germ cell loss. Moreover, compound double heterozygous (R702C/E1841K and D1424/E1841K) males show the same abnormalities in testes as E1841K homozygous males. Conditional ablation of either NM2A or NM2B alone in Sertoli cells has no effect on fertility and testis size, however deletion of both NM2A and NM2B in Sertoli cells results in infertility. Isolation of mutant E1841K Sertoli cells reveals decreased NM2A and F-actin colocalization and thicker NM2A filaments. Furthermore, AE1841K/AE1841K and double knockout Sertoli cells demonstrate microtubule disorganization and increased tubulin acetylation, suggesting defects in the microtubule cytoskeleton. Together, these results demonstrate that NM2A and 2B paralogs play redundant roles in Sertoli cells and are essential for testes development and normal fertility.

Antecubital Fossa Perforator Flaps for Soft-Tissue Defect Repair of the Anterior Elbow: Anatomical Study and Clinical Application.

BACKGROUND: The antecubital fossa is a main perforator cluster region located beside the anterior elbow defect, rendering it crucial to harvest the perforator pedicled flaps for the anterior elbow defects. PATIENTS AND METHODS: A total of 30 preserved cadaveric forearms were dissected in order to describe the perforator anatomy in the antecubital fossa. For each perforator, the number, the site of origin, the diameter at its origin, and the trajectory were recorded. In addition, all the patients treated for anterior elbow defects using inferior cubital artery (ICA) perforator pedicled flaps between June 2013 and June 2018 were reviewed in this retrospective study. RESULTS: A total of 85 perforators were dissected in the antecubital fossa area from the 30 specimens. Among these, 65 perforators originated from the radial artery, 6 from the recurrent radial artery, 13 from the brachial artery, and 1 from the ulnar artery. Each forearm specimen had a constant and large ICA perforator. All perforators originated from source vessels 2-5 cm distal from the interepicondylar line and could be harvested as perforator pedicled flap for anterior elbow reconstruction. In the clinical study, 11 patients with anterior elbow defects were treated with ICA perforator pedicled flaps with satisfactory functional and aesthetic outcomes. CONCLUSION: The antecubital fossa has a constant and dominant ICA perforator and many other perforators. The pedicled antecubital fossa perforator flaps could be harvested flexibly with a reliable blood supply for anterior elbow reconstruction.

Impact of COVID-19 outbreak on the care of patients with inflammatory bowel disease: A comparison before and after the outbreak in South China.

BACKGROUND AND AIMS: Epidemics pose a great challenge to health care of patients. However, the impact of unprecedented situation of COVID-19 outbreak on health care of inflammatory bowel disease (IBD) patients in real-world setting has seldom been investigated. METHODS: We performed an observational study in a tertiary referral IBD center in China. The mode of health care and medication use was compared before and after COVID-19 outbreak. Electronic questionnaire surveys were performed among gastroenterologists and IBD patients to investigate the impact of COVID-19 outbreak on their attitudes towards telemedicine. RESULTS: COVID-19 outbreak resulted in substantial decrease of patients participating in standard face-to-face visit during 1 month post-outbreak (n = 51) than pre-outbreak (n = 249), whereas the participation in telemedicine was significantly higher than comparable period in 2019 (414 vs 93). During the 1 month after COVID-19 outbreak, 39 (39/56, 69.6%) patients had their infliximab infusion postponed with the mean delay of 3 weeks. The immunomodulator use was similar between pre-outbreak and post-outbreak. Six elective surgeries were postponed for a median of 43 days. In post-outbreak period, 193 (193/297, 64.98%) of the surveyed physicians have used telemedicine with an increase of 18.9% compared with 46.13% (137/292) in the pre-outbreak period (P < 0.001); 331 (331/505, 65.54%) of the surveyed IBD patients supported that the use of telemedicine should be increased in future health care. CONCLUSION: COVID-19 outbreak resulted in a great change in health-care access among IBD patients including decrease in standard face-to-face visit and delay of biologics use. There was an increased use and need of telemedicine after COVID-19 outbreak.

Parallel assembly of actin and tropomyosin, but not myosin II, during de novo actin filament formation in live mice.

Many actin filaments in animal cells are co-polymers of actin and tropomyosin. In many cases, non-muscle myosin II associates with these co-polymers to establish a contractile network. However, the temporal relationship of these three proteins in the de novo assembly of actin filaments is not known. Intravital subcellular microscopy of secretory granule exocytosis allows the visualisation and quantification of the formation of an actin scaffold in real time, with the added advantage that it occurs in a living mammal under physiological conditions. We used this model system to investigate the de novo assembly of actin, tropomyosin Tpm3.1 (a short isoform of TPM3) and myosin IIA (the form of non-muscle myosin II with its heavy chain encoded by Myh9) on secretory granules in mouse salivary glands. Blocking actin polymerization with cytochalasin D revealed that Tpm3.1 assembly is dependent on actin assembly. We used time-lapse imaging to determine the timing of the appearance of the actin filament reporter LifeAct-RFP and of Tpm3.1-mNeonGreen on secretory granules in LifeAct-RFP transgenic, Tpm3.1-mNeonGreen and myosin IIA-GFP (GFP-tagged MYH9) knock-in mice. Our findings are consistent with the addition of tropomyosin to actin filaments shortly after the initiation of actin filament nucleation, followed by myosin IIA recruitment.

Modified Anterior Tibial Artery Perforator-Pedicled Propeller Flap for Soft-Tissue Coverage of the Ankle and Heel.

BACKGROUND: The ankle and heel are challenging regions to reconstruct functionally. Here, we explored the feasibility and clinical outcomes of a modified anterior tibial artery perforator-pedicled propeller flap for the repair of soft-tissue defects of the ankle and heel. PATIENTS AND METHODS: Between January 2013 and December 2015, 12 patients with soft-tissue defects of the ankle and/or heel underwent reconstructive surgery that included our flap technique. The flaps measured 20 × 8 cm to 7 × 4 cm. A hand-held Doppler was used to identify a proper constant perforator in the distal ankle. In each case, the base of the flap was well preserved. The flap was transposed (180° rotation) to reach and cover the defect. RESULTS: The average follow-up time was 13 months (10-28 months). We observed good texture matches and contour in all of the flaps. All patients could walk and wear normal footwear. All but one flap survived completely without complications. Partial loss was observed in one patient, and the necrotic region was healed with secondary intention. CONCLUSION: Our modified anterior tibial artery free-style perforator-pedicled propeller flap provides a novel option for functional ankle and heel reconstruction. LEVEL OF EVIDENCE: Level IV.

MitoRACE: evaluating mitochondrial function in vivo and in single cells with subcellular resolution using multiphoton NADH autofluorescence.

KEY POINTS: We developed a novel metabolic imaging approach that provides direct measures of the rate of mitochondrial energy conversion with single-cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE). Measures of mitochondrial NADH flux by mitoRACE are sensitive to physiological and pharmacological perturbations in vivo. Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells with potential for broad applications in the study of energy metabolism. ABSTRACT: Mitochondria play a critical role in numerous cell types and diseases, and structure and function of mitochondria can vary greatly among cells or within different regions of the same cell. However, there are currently limited methodologies that provide direct assessments of mitochondrial function in vivo, and contemporary measures of mitochondrial energy conversion lack the spatial resolution necessary to address cellular and subcellular heterogeneity. Here, we describe a novel metabolic imaging approach that provides direct measures of mitochondrial energy conversion with single-cell and subcellular resolution by evaluating NADH autofluorescence kinetics during the mitochondrial redox after cyanide experiment (mitoRACE). MitoRACE measures the rate of NADH flux through the steady-state mitochondrial NADH pool by rapidly inhibiting mitochondrial energetic flux, resulting in an immediate, linear increase in NADH fluorescence proportional to the steady-state NADH flux rate, thereby providing a direct measure of mitochondrial NADH flux. The experiments presented here demonstrate the sensitivity of this technique to detect physiological and pharmacological changes in mitochondrial flux within tissues of living animals and reveal the unique capability of this technique to evaluate mitochondrial function with single-cell and subcellular resolution in different cell types in vivo and in cell culture. Furthermore, we highlight the potential applications of mitoRACE by showing that within single neurons, mitochondria in neurites have higher energetic flux rates than mitochondria in the cell body. Metabolic imaging with mitoRACE provides a highly adaptable platform for evaluating mitochondrial function in vivo and in single cells, with potential for broad applications in the study of energy metabolism.

Preferred Experience of Modifications to Emergency Surgical Treatment for Total Scalp Avulsion With Halo-Vest Head Ring and Quick Hair Removing.

BACKGROUND: Total scalp avulsion is a fairly rear but severe soft tissue injury. Even with microsurgical replantation, the survival rate is still low. In this study, the authors incorporated 2 main modifications (Halo-Vest head ring and quick hair removing) and assessed the surgical outcomes versus those of traditional replantation. METHODS:: Eighteen patients were included in the study who suffered from total scalp avulsion. After consideration of the outcomes from the first 7 patients, the authors modified our surgical procedures and introduced the use of Halo-Vest head ring and quick hair removing in the treatments for the rest 11 patients. The surgical outcomes with both approaches were observed and compared, including the operation time and incidence of scalp necrosis. RESULTS:: The mean debridement time was 3.5 hours in traditional treatment versus 1.68 hours in modified treatment. The mean operative time was 11.14 hours in traditional treatment versus 8.05 hours in modified treatment. After the replantation, in those 7 patients without modifications, there was 1 total scalp necrosis and 6 partial scalp necrosis. In those 11 patients with modifications, there was 1 total scalp necrosis and 1 suffered a partial scalp necrosis, while the scalp survived well in other 9 patients. Classical cases with modified or traditional methods were reported respectively. CONCLUSION: The application of Halo-Vest head ring and quick hair removing provides a reliable method to treat total scalp avulsion. It is safe, technically easy and worth being widely used in the clinical application.

Engineering a Zirconium MOF through Tandem "Click" Reactions: A General Strategy for Quantitative Loading of Bifunctional Groups on the Pore Surface.

Metal-organic frameworks (MOFs) assembled from linkers of identical length but with different functional groups have gained increasing interests recently. However, it is very challenging for precise control of the ratios of different functionalities. Herein, we reported a stable azide- and alkyne-appended Zr-MOF that can undergo quantitative tandem click reactions on the different functional sites, thus providing a unique platform for quantitative loading of bifunctional moieties. As an added advantage, the same MOF product can be obtained via two independent routes. The method is versatile and can tolerate a wide variety of functional groups, and furthermore, a heterogeneous acid-base MOF organocatalyst was synthesized by tandemly introducing both acidic and basic groups onto the predesigned pore surface. The presented strategy provides a general way toward the construction of bifunctional MOFs with a precise control of ratio of different functionalities for desirable applications in future.

Treatment of Xanthelasma Palpebrarum With Intralesional Pingyangmycin.

BACKGROUND: Xanthelasma palpebrarum (xanthelasma) is the most common type of cutaneous xanthoma, and many patients tend to seek medical treatments for cosmetic reasons. Many methods treating xanthelasma have been proposed, but none of these options can be regarded as a perfect solution. OBJECTIVE: To study and evaluate the intralesional injection treatment of xanthelasma with pingyangmycin, which has been widely used as a broad-spectrum antitumor antibiotic. MATERIALS AND METHODS: 21 lesions in 12 patients were treated by intralesional pingyangmycin. Photographs were taken before and after each treatment session. Patients were followed up for 7 to 36 months. RESULTS: All patients except one received satisfactory results after up to 2 sessions. Only 1 patient had a local recurrence 1 year after the treatment. No severe complications such as infection, atrophy, ulceration, or scar were noticed. CONCLUSION: Intralesional pingyangmycin is a cheap, effective, and safe treatment for xanthelasma, which has been well accepted by patients.

Is vaginal mucosal graft the excellent substitute material for urethral reconstruction in female-to-male transsexuals?

PURPOSE: Construction of a neourethra is always considered to be a difficult part in phalloplasty, especially for the female-to-male (FTM) transsexual patients. We report our experience with prefabricated pars pendulans urethrae using vaginal mucosal graft for phalloplasty in FTM transsexuals. MATERIALS AND METHODS: We retrospectively reviewed notes on the 22 FTM patients treated with pedicled-flap phalloplasty with prefabricated pars pendulans urethrae using vaginal mucosal graft between January 2008 and December 2012. Surgical outcome, urological function, and complications were recorded. Histological difference between normal mucosa and skin, and pathological changes of vaginal mucosal graft were also observed. RESULTS: All the reconstructive penis survived, and patients could void in a standing position finally at a median follow-up of 25.4 ± 6.0 months. Urethral fistula and urethral stricture rates were 31.8 % (7/22 patients) and 4.5 % (1/22 patients), respectively. The occurrence of the urethral stricture was remarkably low compared with previous reports. Our histological results also showed a pronounced similarity between vaginal and buccal mucosa. Morphologically, they resembled urethral epithelium more closely than the forearm skin. Following the free transfer, the vaginal mucosal graft also showed a good revascularization and the inflammatory reaction and the extent of fibrosis of the mucosa decreased to the normal level after a 6-month prefabrication. CONCLUSION: With prefabrication of vaginal mucosal graft, we reconstruct a competent phallic neourethra in these FTM transsexuals. According to its histological similarities and source character, the vaginal mucosa is the excellent substitute material for promising urethral reconstruction in FTM transsexuals.

Nonmuscle myosin II exerts tension but does not translocate actin in vertebrate cytokinesis.

During vertebrate cytokinesis it is thought that contractile ring constriction is driven by nonmuscle myosin II (NM II) translocation of antiparallel actin filaments. Here we report in situ, in vitro, and in vivo observations that challenge this hypothesis. Graded knockdown of NM II in cultured COS-7 cells reveals that the amount of NM II limits ring constriction. Restoration of the constriction rate with motor-impaired NM II mutants shows that the ability of NM II to translocate actin is not required for cytokinesis. Blebbistatin inhibition of cytokinesis indicates the importance of myosin strongly binding to actin and exerting tension during cytokinesis. This role is substantiated by transient kinetic experiments showing that the load-dependent mechanochemical properties of mutant NM II support efficient tension maintenance despite the inability to translocate actin. Under loaded conditions, mutant NM II exhibits a prolonged actin attachment in which a single mechanoenzymatic cycle spans most of the time of cytokinesis. This prolonged attachment promotes simultaneous binding of NM II heads to actin, thereby increasing tension and resisting expansion of the ring. The detachment of mutant NM II heads from actin is enhanced by assisting loads, which prevent mutant NM II from hampering furrow ingression during cytokinesis. In the 3D context of mouse hearts, mutant NM II-B R709C that cannot translocate actin filaments can rescue multinucleation in NM II-B ablated cardiomyocytes. We propose that the major roles of NM II in vertebrate cell cytokinesis are to bind and cross-link actin filaments and to exert tension on actin during contractile ring constriction.

Mouse models of MYH9-related disease: mutations in nonmuscle myosin II-A.

We have generated 3 mouse lines, each with a different mutation in the nonmuscle myosin II-A gene, Myh9 (R702C, D1424N, and E1841K). Each line develops MYH9-related disease similar to that found in human patients. R702C mutant human cDNA fused with green fluorescent protein was introduced into the first coding exon of Myh9, and D1424N and E1841K mutations were introduced directly into the corresponding exons. Homozygous R702C mice die at embryonic day 10.5-11.5, whereas homozygous D1424N and E1841K mice are viable. All heterozygous and homozygous mutant mice show macrothrombocytopenia with prolonged bleeding times, a defect in clot retraction, and increased extramedullary megakaryocytes. Studies of cultured megakaryocytes and live-cell imaging of megakaryocytes in the BM show that heterozygous R702C megakaryocytes form fewer and shorter proplatelets with less branching and larger buds. The results indicate that disrupted proplatelet formation contributes to the macrothrombocytopenia in mice and most probably in humans. We also observed premature cataract formation, kidney abnormalities, including albuminuria, focal segmental glomerulosclerosis and progressive kidney disease, and mild hearing loss. Our results show that heterozygous mice with mutations in the myosin motor or filament-forming domain manifest similar hematologic, eye, and kidney phenotypes to humans with MYH9-related disease.

Traditional Chinese herbal medicine retention enema combined with perineal massage (THREM): a promising therapeutic strategy for refractory chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS).

Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a debilitating condition characterized by lower urinary tract symptoms and persistent pelvic pain or discomfort lasting for more than three months. Currently available oral drug therapies exhibit limited efficacy in the treatment of CP/CPPS. Therefore, personalized and combination therapies are recommended by Chinese CP/CPPS guidelines, which primarily include traditional Chinese medicine, radiofrequency therapy, urethral lavage, transrectal prostate massage, extracorporeal shock wave therapy. However, a significant number of patients do not respond well to all types of these therapeutic methods. Among those who have sequentially or simultaneously undergone at least three different treatment modalities, in addition to oral medications, for more than 1 year, they are defined as patients with refractory CP/CPPS. This retrospective study aims to evaluate the clinical effect of traditional Chinese herbal medicine retention enema combined with perineal massage (THREM) in managing refractory CP/CPPS. Methods: A total of 20 patients with refractory CP/CPPS, who did not show significant improvement despite receiving multiple conventional treatments, including oral medications, were included in this study. Following THREM therapy, the International Prostate Symptom Score (IPSS), visual analogue scale (VAS), and National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI) quality of life (QoL) score were used to assess treatment efficacy. Results: Six months after THREM therapy, a significant decrease in IPSS, VAS, and QoL scores was observed (P<0.01). Importantly, 85% of the patients experienced a reduction in symptoms of ≥60%, with an average degree of alleviation reaching 70.25%±24.20%. Conclusions: THREM treatment demonstrated excellent efficacy in managing refractory CP/CPPS at least for 6 months. It has promising clinical application prospects. Further research is warranted to validate these results and explore the underlying mechanisms of THREM therapy.

Regulation of the Interface Compatibility of the 3D-Printing Interpenetration Networks Toward Reduced Structure Anisotropy and Enhanced Performances.

Digital light processing three-dimensional (DLP 3D) printing, as a promising manufacturing technology with the capability of fabricating 3D objects with complex shapes, typically develops inconsistent material properties due to the stair-stepping effect caused by weak layer-interface compatibility. Here, we report the regulation of the interface compatibility of the 3D-printing resin with versatile photocuring characteristics and the subsequent mechanical, thermal, and dielectric performances by introducing the interpenetration network (IPN). The preparation procedures, interface structure, flexural and tensile strength, modulus, and dielectric performances of the IPN are presented. The greater penetration depth in 3D printing and the subsequently thermocured epoxy network passing through the printing interface synergistically enhance the interface compatibility of 3D-printing samples, with an unobvious printing texture on the surface of the 3D-printing objects. The mechanical performances of the IPN demonstrate little anisotropy, with a bending strength twice as much as the photosensitive resin. Dynamic mechanical analysis of the IPN indicates that the storage modulus increases by 70% at room temperature and the glass transition temperature (Tg) increases by 57%. The dielectric performance of the IPN demonstrates a 36% decrease in dielectric constant and a 28.4% increase in breakdown strength. Molecular dynamics studies have shown that the IPN takes on higher nonbonded energies and hydrogen bonds than the photosensitive resin, indicating a stronger bonding force between molecular chains, thus leading to better physical properties. These results illustrate the effectiveness of the IPN toward enhanced 3D-printing interlayer compatibility for excellent mechanical, thermal, and electrical performances.

NFYB increases chemosensitivity in glioblastoma by promoting HDAC5-mediated transcriptional inhibition of SHMT2.

Temozolomide (TMZ) is a commonly used chemotherapeutic agent for glioblastoma (GBM), but acquired drug resistance prevents its therapeutic efficacy. We investigated potential mechanisms underlying TMZ resistance and glycolysis in GBM cells through regulation by nuclear transcription factor Y subunit ß (NFYB) of the oncogene serine hydroxymethyltransferase 2 (SHMT2). GBM U251 cells were transfected with NFYB-, SHMT2-, and the potential NFYB target histone deacetylase 5 (HDAC5)-related vectors. Glucose uptake and lactate production were measured with detection kits. CCK-8/colony formation, scratch, Transwell, and flow cytometry assays were performed to detect cell proliferation, migration, invasion, and apoptosis, respectively. The binding of NFYB to the HDAC5 promoter and the regulation of NFYB on HDAC5 promoter activity were detected with chromatin immunoprecipitation and dual-luciferase reporter assays, respectively. NFYB and HDAC5 were poorly expressed and SHMT2 was expressed at high levels in GBM U251 cells. NFYB overexpression or SHMT2 knockdown decreased glucose uptake, lactate production, proliferation, migration, and invasion and increased apoptosis and TMZ sensitivity of the cells. NFYB activated HDAC5 to inhibit SHMT2 expression. SHMT2 overexpression nullified the inhibitory effects of NFYB overexpression on glycolysis and TMZ resistance. Thus, NFYB may reduce tumorigenicity and TMZ resistance of GBM through effects on the HDAC5/SHMT2 axis.

Fasciocutaneous foreskin twin flaps in hypospadias repair: Reconstructing a functional penis with freestyle design.

BACKGROUND: Hypospadias is the most common congenital urological deformity in males; however, there is still no perfect solution or surgical method for one-stage operations to fix proximal hypospadias with ventral penile curvature (VPC). We developed a fasciocutaneous foreskin twin flap technique that can provide freestyle flap designs in hypospadias repair. METHODS: A retrospective study including 26 patients was performed between January 2017 and June 2020. The surgical procedures included VPC correction, skin flap design, transfer and reconstruction. The urethra and shaft were reconstructed by twin flaps in one stage. All patients were followed up until 12 months. RESULTS: All VPC cases were corrected after the operation. The fistula rate was 11.5% (3/26). No meatal stenosis, urethral diverticulum, or stricture was observed. A total of 92.3% (24/26) of patients were satisfied with their penis appearance. CONCLUSIONS: The fasciocutaneous foreskin twin flaps provide freestyle designs in hypospadias repair, which can achieve a one-stage operation for proximal hypospadias with low fistula rates.

Investigation of the Fabrication of Diamond/SiC Composites Using α-Si3N4/Si Infiltration.

Diamond/SiC (Dia/SiC) composites possess excellent properties, such as high thermal conductivity and low thermal expansion coefficient. In addition, they are suitable as electronic packaging materials. This study mainly optimized the diamond particle size packing and liquid-phase silicon infiltration processes and investigated a method to prevent the adhesion of the product to molten silicon. Based on the Dinger-Funk particle stacking theory, a multiscale diamond ratio optimization model was established, and the volume ratio of diamond particles with sizes of D20, D50, and D90 was optimized as 1:3:6. The method of pressureless silicon infiltration and the formulas of the composites were investigated. The influences of bedding powder on phase composition and microstructure were studied using X-ray diffraction and scanning electron microscopy, and the optimal parameters were obtained. The porosity of the preform was controlled by regulating the feeding amount through constant volume molding. Dia/SiC-8 exhibited the highest density of 2.73 g/cm3 and the lowest porosity of 0.6%. To avoid adhesion between the sample and buried powder with the bedding silicon powder, a mixed powder of α-Si3N4 and silicon was used as the buried powder and the related mechanisms of action were discussed.